LOM Oncology Notes

CHAPTER 19 - ONCOLOGY

INTRODUCTION

Cancer is a disease caused by abnormal and excessive growth of cells

in the body. It may occur in any tissue and at any time of life, although cancer occurs most
frequently in older people. Cancer cells accumulate as growths called malignant tumors that
compress, invade, and ultimately destroy the surrounding normal tissue. In addition to
their local growth, cancerous cells spread throughout the body by way of the bloodstream
or lymphatic vessels. In some patients the spread of cancers from their site of origin to
distant organs occurs early in the course of tumor growth and ultimately results in death.

CHARACTERISTICS OF TUMORS

Tumors are masses or growth that arise from normal tissue. They may be either malignant
or benign. There are several differences between benign and malignant tumors.

CHARACTERISTICS BENIGN MALIGNANT

Cells are undifferentiated
Well-differentiated cells and often bear little
that resemble normal cells resemblance to the normal
Cell characteristics
of the tissue from which cells of the tissue from
the tumor originated which
they arose
 Tumor grows by expansion Grows at the periphery and
and does not infiltrate the sends out processes that
Mode of growth
surrounding tissues; usually infiltrate and destroy the
encapsulated surrounding tissues

Rate of growth is variable

and depends on level of
Rate of growth is usually
Rate of growth differentiation; the more
slow
anaplastic the tumor, the
faster its growth
Gains access to the blood
Does not spread by and lymphatic channels
Metastasis
metastasis and metastasizes to other
areas of the body

Is usually a localized
phenomenon that does not
Often causes generalized
cause generalized effects
General effects effects, such as anemia,
unless its location
weakness, and weight loss
interferes with vital
functions

Often causes extensive

tissue damage as the tumor
Does not usually cause
outgrows its blood supply or
tissue damage unless its
Tissue destruction encroaches on blood flow to
location interferes with
the area; may also produce
blood flow
substances that cause cell
damage

Does not usually cause

death unless its location Usually causes death unless
Ability to cause death
interferes with vital growth can be controlled
functions

CARCINOGENS

DNA controls not only the production of new cells but also the cell’s ability to
grow. When a cell divides the DNA material copies itself, so that exactly the
same DNA is passed to two new cells that are formed. This process is called
mitosis or self replication.

DNA sends a molecular message to the cytoplasm of the cell so that proteins
can be made for cellular growth. In the nucleus, a coded message is copied from
 DNA on to another molecule called RNA. RNA travels from nucleus to cytoplasm
carrying the message that directs the formation of specific proteins in the cell.

When a cell becomes malignant, their DNA stops making the codes that allow
cells to carry on normal function and instead makes new signals that lead to
movement of cells, invasion of adjacent tissue, and metastasis. Once these
changes are established in a cell, they are passed on to its daughter cells. Such
an inheritable change in a cell is called a mutation. Cellular mutations thus lead
to malignant growths.

ENVIRONMENTAL AGENTS

Agents from the environment, such as chemicals, drugs, tobacco smoke,

radiation, and viruses, can cause damage to DNA and thus produce cancer. These
environmental agents are called carcinogens.

Chemical carcinogens are found in a variety of products and drugs,

including hydrocarbons—in cigarette, cigar, and pipe smoke and automobile exhaust—
insecticides, dyes, industrial chemicals, insulation, and hormones.

Radiation, whatever its source—sunlight, x-rays, radioactive substances—

consists of waves of energy. When this energy interacts with DNA, it causes DNA damage
and mutations that lead to cancer. Ultraviolet radiation in sunlight can cause skin cancer,
especially in persons with lightly pigmented, or fair, skin.

Some viruses are carcinogenic. For example, the human T cell leukemia virus
(HTLV) causes a form of leukemia in adults.

HEREDITY

Cancer may be caused by not only environmental factors but also inherited
factors. Susceptibility to some forms of cancer is transmitted from parents to offspring
through defects in the DNA of the egg or sperm cells.
 In many cases, it is believed that these tumors arise because of inherited or
acquired abnormalities in certain genes called suppressor genes. In normal persons, these
suppressor genes regulate growth, promote differentiation, and suppress oncogenes
from causing cancer. Loss of a normal suppressor gene takes the brake off the process of
cell division and leads to cancer.
CLASSIFICATION OF CANCEROUS TUMORS

Almost half of all cancer deaths are caused by malignancies that originate in lung, breast,
or colon; however, in all there are more than 100 distinct types of cancer. It is possible to
divide these types of cancer into three broad groups on the basis of histogenesis that is,
by identifying the particular type of tissue (hist/o) from which the tumor cells arise (-
genesis). These major groups are carcinomas, sarcomas, and mixed-tissue tumors.

CARCINOMAS

Carcinomas, the largest group, are solid tumors that are derived from
epithelial tissue that lines external and internal body surfaces, including skin, glands, and
digestive, urinary, and reproductive organs. Approximately 90% of all malignancies are
carcinomas.

Malignant Tumor (Carcinomas)

Malignant Tumor (Carcinomas)

Type of Epithelial Tissue

Gastrointestinal tract
Colon Adenocarcinoma of the colon
Liver Hepatocellular carcinoma (hepatoma)
Esophagus Esophageal carcinoma
Stomach Gastric adenocarcinoma
Kidney and bladder Renal cell carcinoma (hypernephroma)
Transitional cell carcinoma of the bladder
Lung Adenocarcinoma (bronchioloalveolar),Large
cell carcinoma, Squamous cell (epidermoid)
Adenocarcinoma of the uterus,Carcinoma of
the penis
Reproductive organs Cystadenocarcinoma (mucinous or serous) of
the ovaries
) Squamous cell (epidermoid) carcinoma of the
vagina or cervix
Skin

Basal cell layer Basal cell carcinoma

Melanocyte
Malignant melanoma

Squamous cell layer Squamous cell

Squamous cell carcinoma
carcinoma

SARCOMAS

Sarcomas also are malignant tumors but are less common than carcinomas. They
derive from connective tissues in the body, such as bone, fat, muscle, cartilage, and bone
marrow and from cells of the lymphatic system. Sarcoma account for approximately 5% of
all malignant neoplasm

Type of Connective Tissue Malignant Tumor

Osteosarcoma (osteogenic sarcoma), Ewing
Bone
sarcoma
Muscle

Smooth (visceral) muscle

Leiomyosarcoma

Striated (skeletal) muscle Rhabdomyosarcoma

Cartilage Chondrosarcoma
Fibrous tissue Fibrosarcoma
Blood vessel tissue Angiosarcoma
Blood-forming tissue
Leukocytes Leukemias

Hodgkin disease
Lymphocytes
Non-Hodgkin lymphomas:
Plasma cells (bone marrow) Multiple myeloma
Nerve tissue
Embryonic nerve tissue Neuroblastoma
Astrocytoma (tumor of glial cells called
Glial tissue astrocytes)
Glioblastoma multiforme
MIXED-TISSUE TUMORS

Mixed-tissue tumors are derived from tissue that is capable of differentiating into both
epithelial and connective tissue. These uncommon tumors are thus composed of several
different types of cells. Examples of mixed-tissue tumors are found in the kidney,
ovaries, and testes.

Types of Tissue Malignant Tumor

Kidney Wilm’s tumor (embryonal adenosarcinoma)
Teratoma (tumor composed of bone, muscle, skin, gland cells
Ovaries and testes
cartilage, etc.)

PATHOLOGICAL DESCRIPTIONS

Cystic: Forming large open spaces filled with fluid. Mucinous tumors are filled with mucus
(thick, sticky fluid) and serous tumors are filled with a thin, watery fluid resembling
serum.

Fungating: Mushrooming pattern of growth in which tumor cells pile one on top of another
and project from a tissue surface. Tumors found in the colon are of this type.

Inflammatory: Having the features of inflammation; that is, redness, swelling and heat.
These tumors characteristically occur in the breast.

Medullary: Pertaining to large, soft, fleshy tumors. Thyroid and breast tumors may be
medullary.

Necrotic: Containing dead tissue. Any type of tumor can outgrow its blood supply and
undergo necrosis.

Polypoid: Growths that are like projections extending outward from base. Sessile polypoid
tumors extend from a broad base and pedunculated polypoid tumors extend from a stem
or stalk. Both benign and malignant tumors of the colon may grow as polyps.

Ulcerating: Characterized by an open, exposed surface resulting from death of overlying

tissue. Ulcerating tumors are often found in the stomach, breast, colon, and skin.
Verrucous: Resembling a wart-like growth. Tumors of the gingival (cheek) are frequently
verrucous.

MICROSCOPIC DESCRIPTIONS

Alveolar: Tumor cells form patterns resembling small, microscopic sacs; commonly found in
tumors of muscle, bone, fat, and cartilage.

Carcinoma in situ: Referring to localized tumor cells that have invaded adjacent
structures. Cancer of the cervix may begin as carcinoma in situ.

Diffuse: Spreading evenly throughout the affected tissue. Malignant lymphomas may
display diffuse involvement of lymph nodes.

Dysplastic: Pertaining to abnormal formation of cells. These tumors display a highly

abnormal but not clearly cancerous appearance. Dysplastic nevi (moles on skin) are example.
Epidermoid: Resembling squamous epithelial cells (thin, plate-like), often occurring in the
respiratory tract.

Follicular: Forming small, microscopic, gland-type sacs. Thyroid gland cancer is an example.

Nodular: Forming multiple areas of tightly packed clusters of cells with lightly populated
areas in between. Malignant lymphomas may display a nodular pattern of lymph node
involvement.

Papillary: Forming small, finger-like or nipple-like projections of cells. Bladder cancer may
be described as papillary.

Pleomorphic: Composed of variety of types of cells. Mixed-cell tumors are examples.

GRADING SYSTEM

Tumors are classified on the basis of tissue of origin, microscopic

appearance, and extent of spread. Of particular importance are the tumor’s grade
(its degree of maturity or differentiation under the microscope) and its stage (its
extent of spread within the body). These two properties influence the prognosis (the
chances of successful treatment and survival) and determine the specific treatment to
be used.
 When grading a tumor, the pathologist is concerned with the
microscopic appearance of the tumor cells, specifically with their degree of maturation or
differentiation. Often, three or four grades are used. Grade I tumors are very well
differentiated, so that they closely resemble cells from the normal parent tissue of
their origin. Grade IV tumors are so undifferentiated or anaplastic that even recognition
of the tumor’s tissue of origin may be difficult. Grades II and III are intermediate in
appearance, moderately or poorly differentiated, as opposed to well differentiated
(grade I) and undifferentiated (grade IV).

Patients with grade I tumors have a high survival rate, and patients with grade II, III, and
IV tumors have an increasingly poorer survival rate.

STAGING SYSTEM

The staging of cancerous tumors is based on the extent of spread of the tumor. It relies
on careful definition of the size and spread of the tumor, using CT, PET/CT, and MRI scans
and radionuclide (radioactive) bone scans.

An example of a staging system is the tumor-node-metastasis (TNM) International Staging

System. It has been applied to malignancies such as lung cancer, as well as to many other
tumors. In this staging system, T specifies the size and degree of local extension of the
tumor; N is the number of regional lymph nodes that have been invaded by tumor; and M
specifies the presence or absence of metastases (spreads to distant sites) of the tumor
cells. Numbers denote size and degree of involvement: For example, 0 indicates
undetectable, and 1, 2, 3, and 4, a progressive increase in size or involvement.
TNM staging may be based on clinical data (physical examination and radiologic
assessment) or actual histopathologic evaluation of the tumor and adjacent lymph
nodes. In some cases, bone marrow, liver, or other tissues are biopsied to confirm
metastases.
CANCER TREATMENT

Four major approaches to cancer treatment are surgery, radiation therapy, chemotherapy,
and biological therapy. Each method (modality) may be used alone, but often they are
coordinated in combined modality programs to improve the overall treatment result.
SURGERY

In many patients with cancer, the tumor is discovered before it has spread, and it may be
cured by surgical excision.

The following is a list of terms that describe surgical procedures used in diagnosing and
treating cancer.

Process of burning tissue to destroy it. Examples are electro

Cauterization cauterization (using a needle or snare heated by electric current),
laser, dry ice, and chemicals.
Core needle biopsy Placement of a large-bore needle that extracts a thin core of tissue.

Cryosurgery Use of subfreezing temperature to destroy tissue.

Tumor is removed along with a large area of surrounding tissue

En bloc resection containing lymph nodes. Modified radical mastectomy, colectomy, and
gastrectomy are examples.
Removal of tumor and a margin of normal tissue. This procedure
Excisional biopsy provides a specimen for diagnosis and may be curative for small
noninvasive tumors.
Wide resection involving removal of the tumor, its organ of origin,
and all surrounding tissue in the body space. Pelvic exenteration with
Exenteration removal of the uterus, ovaries, bladder, and segments of the large
bowel may be performed to treat large primary tumors of the
uterus.
Fine needle Placement of a very thin needle inside the tumor mass and
aspiration extracting cells for microscopic evaluation.
Destruction of tissue by electric sparks generated by a high-
Fulguration
frequency current.
Piece of tumor is removed for examination to establish a diagnosis.
More extensive surgical procedure or other forms of treatment,
Incisional biopsy
such as chemotherapy or radiation therapy, are then used to treat
the bulk of the tumor.
RADIATION THERAPY

The goal of radiation therapy (RT) is to deliver a maximal dose of ionizing

radiation to the tumor tissue and a minimal dose to the surrounding normal tissue. High-
dose irradiation (exposure of tissue to radiation) destroys tumor cells and produces
damage to DNA. Newer techniques of irradiation use high-energy beams of protons (sub-
atomic particles) to improve the uniformity (conformality) of dose and to limit damage to
normal tissues.

Terms used in the field of radiation therapy for cancer are as follows:

Electron beams Low-energy beams for treatment of skin or surface tumors.

Fractionation A method of dividing radiation into small, repeated doses rather than
fewer large doses. Fractionation allows larger total doses to be given
while causing less damage to normal tissue.
Linear accelerator Large electronic device that produces high-energy x-ray (or photon)
beams for the treatment of deep-seated tumors. Intra operative
radiation therapy (IORT) is direct application of radiation during
surgery using a linear accelerator in the operating room.
Radiocurable Tumor that can be completely eradicated by radiation therapy.
tumor Usually, this is a localized tumor with no evidence of metastasis.
Radioresistant Tumor that requires large doses of radiation to produce death of the
tumor cells. Melanoma and renal carcinoma are the most radioresistant.
Radiosensitive Tumor in which irradiation can cause the death of cells without
tumor serious damage to surrounding tissue.
Radiosensitizers Drugs that increase the sensitivity of tumors to x-rays. Many cancer
chemotherapy drugs, especially 5-fluorouracil and cisplatin, sensitize
tumors and normal tissue to radiation, thereby improving the outcome
of treatment.
Stereotactic Single large dose of radiation (Gamma Knife surgery) delivered from
radiosurgery several different angles under stereotactic (highly precise) guidance
to
destroy a vascular abnormality or to treat small intracranial tumors
CHEMOTHERAPY

Cancer chemotherapy is the treatment of cancer using chemicals (drugs). It is

the standard treatment for many types of cancer, and it produces cures in most
patients who have testicular cancer, acute lymphocytic leukemia (children), and
Hodgkin disease. Chemotherapy may be used alone or in combination with surgery and
irradiation to improve cure rates.

Combination chemotherapy is the use of two or more antitumor drugs together to kill a
specific type of malignant growth.

The following are categories of cancer chemotherapeutic agents.

Alkylating agents These are synthetic compounds containing one or two alkyl
groups. The chemicalsinterfere with the process of DNA
synthesis by attaching to DNA molecules.

Antibiotic These drugs are produced by bacteria or fungi. Most act by

binding to DNA in the cell, thus promoting DNA strand breaks
and preventing the replication or copying of DNA.

Antimetabolites These drugs inhibit the synthesis of substance that are the
necessary components of DNA or may directly block the
replication or copying of DNA.

Antimitotics These chemicals are derived from bacteria, fungi, or plants

or from animals found on coral reefs or in the ocean. Paclitaxel
(Taxol) and the vinca alkaloids are isolated from plants and
block the function of the cell structural protein, the
microtubule, which is essential for mitosis. They are used
frequently in combination with other chemotherapeutic agents.

Hormonal agents Hormones are a class of chemicals made by endocrine glands in

the body. Example are estrogens made in the ovaries and
androgens made in the testes and adrenal glands. Hormones
attach to receptor proteins in target tissues. The hormone-
receptor complex stimulates certain normal tissues, such as
breast or uterine lining cells, to divide and grow.
Biological Therapy

Another approach to cancer treatment is to use the body’s own

defenses to fight tumor cells. Investigators are exploring how the elements of the immune
system can be restored, enhanced, mimicked, and manipulated to destroy cancer cells.
Substances produced by normal cells that directly block tumor growth or that stimulate
the immune system and other body defenses are called biological response modifiers.

Examples of these substances are interferons (made by lymphocytes),

monoclonal antibodies (made by mouse or human immune cells and capable of binding to
human tumors), colony-stimulating factors (CSFs) that stimulate blood-forming cells to
combat the myelosuppressive side effects of chemotherapy, and interleukins that
stimulate the immune system to destroy tumors.
VOCABULARY

Adjuvant therapy: Assisting primary treatment. Drugs are given early in the course of
treatment, along with surgery or radiation to attack cancer cells that may be too small to
be detected by diagnostic techniques.

Ankylating agents: Synthetic chemicals containing alkyl groups that interfere with DNA
synthesis.

Anaplasia: Loss of differentiation of cells; reversion to a more primitive cell type.

Antibiotics: Chemical substances produced by bacteria that inhibit the growth of cells;
used in cancer chemotherapy.

Antimetabolites: Chemicals that prevent cell division by inhibiting the formation of

substances necessary to make DNA; used in cancer chemotherapy.

Apoptosis: Programmed cell death. Normal cells undergo apoptosis when they are damaged
or aging. Some cancer cells have lost the ability to undergo apoptosis and live forever.

Benign: Noncancerous.

Biological response modifiers: Substances produced by normal cells that either directly
block tumor growth or stimulate the immune system.

Biological therapy: Use of the body’s own defense mechanisms to fight tumor cells.

Carcinogens: Agents that cause cancer; chemicals, drugs, radiation and viruses.

Carcinoma: Cancerous tumor made up of cells of epithelial origin.

Cellular oncogens: Pieces of DNA that when broken or dislocated can cause a normal cell
to become malignant.

Chemotherapy: Treatment with drugs.

Combination chemotherapy: Use of several chemotherapeutic agents together in the

treatment of tumors.

Dedifferentiation: Loss of differentiation of cells.

Deoxyribonucleic acid (DNA): Genetic material within the nucleus of a cell; controls cell
division and protein synthesis.

Differentiation: Specialization of cells.

Electron beams: Low-energy beams of radiation for treatment of skin or surface tumors.

Encapsulated: Surrounded by a capsule; benign tumors are encapsulated.

Fractionation: Giving radiation in small repeated doses.

Grading of tumors: Evaluating the degree of maturity of tumor cells.

Gross description of tumors: Visual appearance of tumors; cystic, fungating,

inflammatory, medullary, necrotic, polypoid, ulcerating and verrucous.

Infiltrative: Extending beyond normal tissue boundaries.

Invasive: Having the ability to enter and destroy surrounding tissue.

Linear accelerator: Device that produces high-energy x-ray beams for treatment of
deep-seated tumors.

Malignant: Tending to become worse and result in death; tumors having the
characteristics of invasiveness, anaplasia, and metastasis.

Metastasis: Spread of a malignant tumor to a secondary site; literally, beyond control.

Microscopic description of tumors: The appearance of tumors as seen under the

microscope; alveolar, carcinoma in situ, diffuse, dysplastic, epidermoid, follicular, nodular,
papillary, pleomorphic, undifferentiated.

Mitosis: Replication of cells; a stage in the cell life cycle involving the production of two
identical cells from a parent cell.Met

Mixed-tissue tumors: Tumors composed of different types of tissue.

Modality: Method of treatment such as surgery, chemotherapy or radiation.

Morbidity: The condition of being diseased.

Mucinous: Containing mucus.

Mutation: Change in the genetic material of a cell; may be caused by chemicals, radiation
or viruses or may occur spontaneously.

Neoplasm: New growth; benign or malignant tumors.

Oncogene: A region of DNA found in tumor cells (cellular oncogene) or in viruses that
cause cancer.

Pedunculated: Possessing a stem or stalk (peduncle); characteristic of some polypoid

tumors.

Pharmacokinetics: Study of distribution and removal of drugs in the body over a period of
time.

Protocol: An explicit detailed plan for treatment.

Radiation: Energy carried by a stream of particles. Various forms of radiation can cause
cancer.

Radiocurable tumor: Cells that are eradicated by radiation therapy.

Radioresistant tumor: Cells that require large doses of radiation to be destroyed.

Radiosensitive tumor: A tumor in which radiation can cause death of cells.

Radiosensitizers: Drugs that increase the sensitivity of tumors to x-rays.

Radiotherapy: Treatment using radiation.

Relapse: Return of symptoms of disease.

Remission: Absence of symptoms of disease.

Ribonucleic acid: Cellular substance that along with DNA plays an important role in the
synthesis of proteins in cells.

Sarcoma: Cancerous tumor derived from connective tissue.

Serous: Pertaining to a thin, watery fluid (serum).

Sessile: Having no stem; characteristic of some polypoid tumors.

Solid tumor: Tumor composed of mass of cells.

Staging of tumors: System of evaluating the extent of spread of tumors.

Steroids: Complex, naturally occurring chemicals such as hormones that are used as
chemotherapeutic agents.

Surgical procedures to treat cancer: Methods of removing cancerous tissue;

cryosurgery, electrocauterization, en bloc resection, excisional biopsy, exenteration,
fulguration, incisional biopsy.

Ultraviolet radiation: Rays given off by the sun.

Viral oncogenes: Pieces of DNA from viruses that infect a normal cell and cause it to
become malignant.

Virus: An infectious agent that reproduces by entering a host cell and using the host’s
genetic material to make copies of itself.
LABORATORY TESTS

These tests measure proteins produced by tumors. Some are present in the
bloodstream whereas others are measured in the tumor itself.

Acid phosphatase: Enzyme found in high concentration in the blood of patients with
prostate cancer.

Alpha-fetoprotein test: Detects the presence in serum of alpha-fetoprotein, which is

found in patients with liver and testicular cancer.

Beta-HCG test: Detects human chorionic gonadotropin in the serum of patients with
testicular cancer.

CA-125: Cell surface protein produced by ovarian cancer cells.

CEA test: Detects carcinoembryonic antigen in the bloodstream of patients with tumors
of GI origin.

Estrogen (estradiol) receptor assay: Measures the concentration of estrogen receptor

sites in tumor cells of breast cancer patients.

Prostate specific antigen (PSA): A protein produced by prostate cancer cells and found
in the bloodstream.
CLINICAL PROCEDURES

Bone marrow biopsy: A small amount of bone marrow tissue is aspirated and examined
under the microscope for evidence of cancerous cells.

Exfoliative cytology: Cells are scraped from the region of suspected disease and
examined under the microscope. The Pap smear is an example.

Lymphangiography: Contrast dye is injected into the lymphatic vessels of the feet and x-
rays are taken of the lymphatic system to detect enlarged lymph nodes, blockage of the
lymphatic system and the presence of tumors.

Needle biopsy: A needle is inserted into the tissue in question and a core of tissue is
removed. Aspiration may be used to withdraw free cells from a fluid-filled cavity such as
in cystic areas of the breast or from a solid lump of tumor.

Peritoneoscopy: This procedure (also called laparoscopy) is used to inspect the abdominal
cavity for tumors. A laparascope (peritoneoscope) is inserted into the peritoneal cavity
through a small incision in the abdominal wall.

Staging laparotomy: This is a wide surgical incision of the abdomen that allows the
physician to explore the abdominal cavity to determine the extent of malignant disease.

Radionuclide scans: Radioactive substances (called radionuclides) are injected

intravenously and pictures are taken of the organs in question. In liver and spleen scans,
irregular distribution of radioactivity or absence of radioactivity indicates possible liver
disease whereas on bone scans abnormal areas of concentration of radioactivity may
indicate bone destruction and repair, processes that are associated with metastasis.
Abnormalities in brain scans appear as increased accumulation of radioactivity. Normal
brain tissue does not take up radioactivity because of blood-brain barrier).
ABBREVIATIONS

Bx: Biopsy

Ca: Cancer

CEA: Carcinoembryonic antigen

chem.: Chemotherapy

CR: Complete response

DNA: Deoxyribonucleic acid

ER: Estrogen receptor

5-FU: 5-fluorouracil

Ga: Gallium

mets: Metastasis

NED: No evidence of disease

NHL: Non-Hodgkin’s lymphoma

PR: Partial response

PSA: Prostate specific antigen

RNA: Ribonucleic acid

TNM: Tumor, nodes, metastases

XRT: Radiation therapy